Association between parental decisions regarding abortion and severity of fetal heart disease.

The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes. Therefore, we investigated risk factors associated with parents' decision-making regarding abortion following a prenatal diagnosis of fetal heart disease. Our analysis included 73 (terminated: n = 37; continued: n = 36) pregnancies with a fetal heart disease diagnosed before 22 weeks of gestation. Increased gestational age at diagnosis reduced the likelihood of parents' decision on termination (Model 1: adjusted odds ratio, 0.94; 95% confidence interval 0.89-0.99; Model 2: 0.95 0.90-0.997). Critical disease (5.25; 1.09-25.19) and concurrent extracardiac or genetic abnormalities (Model 1: 4.19, 1.21-14.53; Model 2: 5.47, 1.50-19.96) increased the likelihood of choosing abortion. Notably, complex disease did not significantly influence parental decisions (0.56; 0.14-2.20). These results suggest that parental decision-making regarding abortion may be influenced by earlier gestational age at diagnosis, the lethality of heart disease, and extracardiac or genetic abnormalities, but not its complexity if prenatal diagnosis and parental counseling are provided at a cardiovascular-specialized facility.

Comprehensive Cardiac Rehabilitation Following Acute Myocardial Infarction Improves Clinical Outcomes Regardless of Exercise Capacity.

BACKGROUND: Reduced exercise capacity is a prognostic indicator of adverse outcomes in patients with acute myocardial infarction (AMI). However, few studies have evaluated the effectiveness of comprehensive cardiac rehabilitation (CR) in this population. This study aimed to clarify the efficacy of comprehensive CR in patients with AMI and reduced exercise capacity.Methods and Results: This cohort study included 610 patients with AMI who underwent percutaneous coronary intervention. Major adverse cardiovascular events (MACE) were compared between patients who participated in comprehensive outpatient CR for 150 days (CR group; n=430) and those who did not (non-CR group; n=180). During the mean (±SD) follow-up period of 6.1±4.0 years, the CR group exhibited a lower incidence of MACE (log-rank P=0.002). Multivariable analysis revealed that Killip classification, diuretics at discharge, and participation in comprehensive CR were independently associated with MACE. The CR group was further divided into 2 groups, namely reduced exercise capacity (% predicted peak V̇O2<80%; n=241) and preserved exercise capacity (≥80%; n=147), based on the initial cardiopulmonary exercise test. Despite distinct exercise capacities, the incidence of MACE was comparable and physical parameters improved similarly after comprehensive CR in both groups. CONCLUSIONS: Comprehensive CR in patients with AMI effectively reduced the incidence of MACE regardless of initial exercise capacity. Cardiologists should actively encourage patients with low exercise capacity to participate in comprehensive CR.

Prognostic factors in patients in the terminal phase of haematological malignancies who are receiving home medical care.

Although there are many prognostic models for patients in the terminal phase of solid tumours, a reliable prognostic scoring system in patients in the terminal phase of haematological malignancies (HM) has not been established. We retrospectively evaluated 180 patients in the terminal phase of HM who were receiving home medical care (HMC). Multivariate analyses revealed that clinician's estimate, consciousness, loss of appetite, dyspnoea, neutrophil count, lymphocyte count, and lactate dehydrogenase were associated with overall survival (OS). Based on this result, we developed a novel prognostic scoring system, the Japan palliative haematological oncology prognostic estimates, in which four risk groups were shown to clearly differ in survival (p < 0.001): a low-risk group (n = 41, median OS of 434 days), an intermediate-low-risk group (n = 80, median OS of 112 days), an intermediate-high-risk group (n = 38, median OS of 31.5 days), and a high-risk group (n = 21, median OS of 10 days). This is the first investigation of prognostic factors that influence the OS of patients in the terminal phase of HM who are receiving HMC. Providing patients with reliable information about their prognosis is important for them to consider how to spend their remaining life.

Polyvascular Disease and the Incidence of Cancer in Patients with Coronary Artery Disease.

Introduction: Based on the possible relation of atherosclerotic cardiovascular disease to the development of cancer, we examined whether polyvascular disease, as a surrogate marker of the severity of atherosclerosis, is associated with the incidence of cancer in patients with coronary artery disease (CAD). Methods: A total of 8,856 patients with CAD between January 2009 and July 2014 were eligible for this observational study. Two cohorts were established based on the presence or absence of polyvascular disease (i.e., polyvascular disease and CAD only) and tracked for the incidence of cancer and all causes of death. Polyvascular disease was defined when accompanied by diagnosed aortic and/or peripheral arterial disease or other arterial diseases at enrollment. Results: With a median follow-up of 1,095 d, the incidence of cancer was markedly higher in the cohort of 716 patients with polyvascular disease than in the cohort of 8,140 patients with CAD only (8.8% vs. 4.9%, P = 0.0001). A large difference in the incidence of cancer was also found in accordance with a number of the coexisting vascular disease with CAD. With the adjustment of shared common risks, polyvascular disease was an independent contributor to the incidence of cancer (hazard ratio, 1.362; 95% confidence interval [CI], 1.029-1.774). In a total of 548 patients (6.2% of participants) died during follow-up, and all-cause, cardiovascular, and cancer mortalities were all higher in the cohort with polyvascular disease than in the cohort with CAD only. Conclusion: The presence of polyvascular disease may be associated with the incidence of cancer in patients with CAD, implying a pivotal role of the severity of atherosclerosis in cancer development (ClinicalTrials.gov. number: NCT04198896).

Delay in seeking treatment before emergent heart failure readmission and its association with clinical phenotype.

BACKGROUND: Many patients with emergent heart failure (HF) readmission have a delay between symptom onset and hospitalization. The present study aimed to characterize the interval between symptom onset and hospitalization in patients being readmitted for HF and to compare the clinical phenotypes of patients with delay before emergent readmission with those who presented to the hospital earlier. METHODS: Data for a total of 2073 consecutive patients was collected from the Tokyo CCU Network database; the patients were divided into delayed (those who sought medical help > 2 days after symptom onset; n = 271) and early groups (remaining patients; n = 1802), and their clinical characteristics and mode of presentation were compared. RESULTS: Age, sex, and laboratory findings including brain natriuretic peptide and serum creatinine levels were not significantly different between the two groups. Patients in the delayed group had greater chronic fluid retention and symptoms not associated with respiratory failure, whereas those in the early group were more likely to have acute respiratory distress, faster heart and respiration rates, and higher systolic blood pressure. CONCLUSIONS: More than one in ten patients with HF readmission delay seeking treatment > 2 days after symptom onset. Patients who delayed seeking treatment showed the phenotype of chronic fluid retention, whereas those who presented to the hospital earlier had the phenotype of acute respiratory failure.

[A Survey on Home Care Needs of Patients with Hematological Diseases].

Home care for patients with hematological diseases is often difficult to coordinate due to the challenges associated with continuous provision of supportive therapies, such as blood transfusions. On the other hand, home care needs of patients with hematological diseases are not clear. In this study, we conducted a questionnaire survey of patients with hematological diseases under home care. Responses were obtained from 605 patients with hematological diseases. Regarding home care, their primary expectation was a reduction in the physical burden caused by hospital visits, while their primary concern was emergency care due to a sudden change in their conditions. More than 90% of the patients stated that they wished to be seen by hematology specialists. In terms of blood transfusions, 53.5% wished to continue receiving a red blood cell transfusion and 53.9% a platelet transfusion at home. Furthermore, 70.9% of the patients stated that palliative chemotherapy was also needed in home care. With respect to emergency care, the highest percentage of patients(56.5%)wanted their home care doctors to treat them first and, if needed, contact their attending doctors at the hospital. This suggests the possibility that "the two-attending doctor system,"a concept that has gained importance in recent years, may also be effective in home care for hematological diseases.

Different prognostic associations of beta-blockers and diuretics in heart failure with preserved ejection fraction with versus without high blood pressure.

OBJECTIVE: No agents have been proven to improve survival in heart failure with preserved ejection fraction (HFpEF), but the phenotypic diversity of HFpEF suggests it may be possible to identify specific HFpEF phenotypes that will benefit from certain treatments. This study compared the risk factors for and prognostic impacts of treatments on in-hospital mortality between HFpEF patients with (+) and without (-) high blood pressure (HBP). METHODS: Data on 2238 consecutive HFpEF patients were extracted from Tokyo CCU Network data registry and analysed. HFpEF was defined as an ejection fraction greater than or equal to 50%; HBP was defined as elevated systolic blood pressure (>140 mmHg) at admission. Potential risk factors for in-hospital mortality were selected by univariate analyses and those with P < 0.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors. RESULTS: In-hospital mortality was significantly lower for HFpEF + HBP than HFpEF - HBP patients (log-rank, P < 0.001). Independent risk factors for in-hospital mortality in HFpEF + HBP patients were older age (hazard ratio 1.069) and in-hospital treatment without beta-blockers (hazard ratio 7.946), whereas older age (hazard ratio 1.035), higher C-reactive protein (hazard ratio 1.047), higher B-type natriuretic peptide (hazard ratio 1.000) and in-hospital treatment without diuretics (hazard ratio 4.201) were identified as independent risk factors in HFpEF - HBP patients. CONCLUSION: There were significant differences in prognostic factors, including beta-blocker and diuretic treatments, for in-hospital mortality between HFpEF patients with and without HBP. These findings suggest possible individualized therapies for patients with HFpEF.

Effects of glycemic control on in-hospital mortality among acute heart failure patients with reduced, mid-range, and preserved ejection fraction.

The relationship between glycemic control and outcome in patients with heart failure (HF) remains contentious. A recent study showed that patients with HF with mid-range ejection fraction (HFmrEF) more frequently had comorbid diabetes relative to other patients. Herein, we examined the association between glycosylated hemoglobin (HbA1c) and in-hospital mortality in acute HF patients with reduced, mid-range, and preserved EF. A multicenter retrospective study was conducted on 5205 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; then, multivariate Cox regression analysis with backward stepwise selection was performed to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 44% (2288 patients) had reduced EF, 20% had mid-range EF, and 36% had preserved EF. The overall in-hospital mortality rate was 4.6%, with no significant differences among the HF patients with reduced, mid-range, and preserved EF groups. For patients with HFmrEF, higher HbA1c level was a significant risk factor for in-hospital mortality (hazard ratio 1.387; 95% confidence interval 1.014-1.899; P = 0.041). In contrast, HbA1c was not an independent risk factor for in-hospital mortality in HF patients with preserved or reduced EF. In conclusion, HbA1c is an independent risk factor for in-hospital mortality in acute HF patients with mid-range EF, but not in those with preserved or reduced EF. Elucidation of the pathophysiological mechanisms behind these findings could facilitate the development of more effective individualized therapies for acute HF.

Impact of Triggering Events on Outcomes of Acute Heart Failure.

BACKGROUND: The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes. METHODS: Consecutive patients hospitalized for acute heart failure between 2010 and 2014 were registered in a multicenter data registration system (72 institutions within Tokyo, Japan). Baseline demographics and in-hospital mortality were extracted from 17,473 patients. Patients with a trigger were grouped based on their triggering event: those with onset during (a) physical activity; (b) sleeping; (c) eating or watching television; (d) bathing or excretion (use of restrooms); and (e) engaging in other activities. These patients were compared with patients without identifiable triggers. Multiple imputation was used for missing data. RESULTS: Patients were predominantly men (57.1%), with a mean age of 76.0 ± 13.0 years; a triggering event was present in 49.1%. No significant difference in baseline characteristics was noted between groups except for younger age, higher blood pressure, and prevalence of signs of congestion in the trigger-positive group. In-hospital mortality rate was 7.9%. Presence of triggers was positively associated with a reduced risk of in-hospital mortality (adjusted odds ratio 0.79; 95% confidence interval, 0.70-0.90; P = .0003). In a delta-adjusted pattern mixture model, the effect of a triggering event on in-hospital mortality remained consistently significant. CONCLUSION: Triggering events for acute heart failure can provide additional information for risk prediction. Efforts to identify the triggers should be made to classify patients according to risk group.

A rotating cerium anode X-ray system allows visualization of intramural coronary vessels after cardiac stem cell therapy for myocardial infarction.

Conventional angiography is insufficient for evaluating the therapeutic effect of cardiac regeneration therapy. A microangiographic X-ray system using a cerium anode was developed. Cerium has a characteristic X-ray with a peak at 34.6 keV, which allows visualization of tiny amounts of iodine. The performance of the cerium anode X-ray system was evaluated in two excised normal canine hearts and in excised ischemic canine hearts treated with c-kit-positive cardiac stem cells (5 canines) or without cells (5 control canines). In the normal canines, branches penetrating from the left anterior descending artery into the myocardium were visualized, down to third-order branches. In just the treated hearts treated with stem cells, small vessels characterized by irregular vessel walls were observed. The cerium anode X-ray system allowed visualization of microvessels in excised ischemic canine hearts, and may evaluate the effect of cardiac stem cell therapy.

Incidence of cancers in patients with atherosclerotic cardiovascular diseases.

BACKGROUND: To address a clinical impact of atherosclerotic cardiovascular diseases (CVD) on cancer developments, we investigated an issue whether any difference in an incidence of cancers is present between patients with atherosclerotic CVD and those with non-atherosclerotic CVD. METHODS: Of a total of 32,095 consecutive patients with acquired CVD enrolled in the Sakakibara Health Integrative Profile cohort study, we segregated patients based on a presence of atherosclerotic or non-atherosclerotic CVD to investigate an incidence of cancers and mortality. We also evaluated an incidence of cancers in patients with a singular presence versus a plural presence of atherosclerotic CVD. Atherosclerotic CVD included coronary artery diseases, aortic diseases and peripheral artery diseases. Non-atherosclerotic CVD were any acquired CVD except atherosclerotic CVD. RESULTS: During a median follow-up of 1020 days (interquartile range, 665-1340 days), an incidence of cancers (5% vs. 2%, p = 0.0001) and overall mortality (6% vs. 3%, p = 0.0001) were more than two-fold higher in 10,592 patients with atherosclerotic CVD than in 21,503 patients with non-atherosclerotic CVD. A presence of atherosclerotic CVD (hazard ratio 1.372 with 95% confidence interval 1.199-1.569) was independently associated with an incidence of cancers. In patients with atherosclerotic CVD, 61 of 640 patients with a plural presence and 470 of 9932 patients with a singular presence developed cancers (9% vs. 5%, p = 0.0001). An incremental risk of death was found according to a presence of atherosclerotic CVD, cancers, and both of them (all p = 0.0001). CONCLUSIONS: A presence of atherosclerotic CVD itself may have a potential risk for cancer developments. TRIAL REGISTRATION: ClinicalTrials.gov. number, NCT03005834.

The proliferative potential of human cardiac stem cells was unaffected after a long-term cryopreservation of tissue blocks.

BACKGROUND: Human c-kit-positive cardiac stem cells (CSCs) have been used to treat patients suffering from ischemic cardiomyopathy. This study aimed to investigate whether a long-term storage of cardiac tissues would influence the growth potential of the subsequently isolated CSCs. METHODS: A total of 34 fresh samples were obtained from various cardiac regions [right atrium (RA), left atrium (LA), and/or left ventricle (LV)] of 21 patients. From 12 of these patients, 18 samples kept frozen for ~2 years were employed to prepare and characterize the CSCs. After confirming the specificity of the cell sorting by c-kit immunolabeling, the growth rate (number of doublings per day), BrdU positivity, and colony forming unit (CFU) were measured in each CSC population; the values were compared among distinct cardiac regions as well as between fresh and frozen tissues from which CSCs were derived. RESULTS: Among independent measurements indicating growth potential, the growth rate and BrdU positivity remarkably correlated in freshly prepared CSCs. The cells obtained from every examined region displayed a high proliferative capacity with the growth rate of 0.48±0.19 and the BrdU positivity of 15.0%±7.6%. The right atrial CSCs tended to show a greater growth than those in the other two areas. Similarly, the CSCs were isolated from tissue blocks, cryopreserved for ~2 years, and compared with CSCs derived from the fresh specimens of the same patients. Importantly, we were able to obtain and culture CSCs from every frozen material, and their proliferative potential, represented by the growth rate of 0.47±0.22 and the BrdU positivity of 13.7%±7.9%, was not inferior to that of the freshly prepared cells. CONCLUSIONS: The long-term cryopreservation of cardiac tissues did not affect the growth potential of the derivative CSCs. Our findings should expand the therapeutic applications of these cells over a longer time span.

Single-cell analysis of the fate of c-kit-positive bone marrow cells.

The plasticity of c-kit-positive bone marrow cells (c-kit-BMCs) in tissues different from their organ of origin remains unclear. We tested the hypothesis that c-kit-BMCs are functionally heterogeneous and only a subgroup of these cells possesses cardiomyogenic potential. Population-based assays fall short of identifying the properties of individual stem cells, imposing on us the introduction of single cell-based approaches to track the fate of c-kit-BMCs in the injured heart; they included viral gene-tagging, multicolor clonal-marking and transcriptional profiling. Based on these strategies, we report that single mouse c-kit-BMCs expand clonally within the infarcted myocardium and differentiate into specialized cardiac cells. Newly-formed cardiomyocytes, endothelial cells, fibroblasts and c-kit-BMCs showed in their genome common sites of viral integration, providing strong evidence in favor of the plasticity of a subset of BMCs expressing the c-kit receptor. Similarly, individual c-kit-BMCs, which were infected with multicolor reporters and injected in infarcted hearts, formed cardiomyocytes and vascular cells organized in clusters of similarly colored cells. The uniform distribution of fluorescent proteins in groups of specialized cells documented the polyclonal nature of myocardial regeneration. The transcriptional profile of myogenic c-kit-BMCs and whole c-kit-BMCs was defined by RNA sequencing. Genes relevant for engraftment, survival, migration, and differentiation were enriched in myogenic c-kit-BMCs, a cell subtype which could not be assigned to a specific hematopoietic lineage. Collectively, our findings demonstrate that the bone marrow comprises a category of cardiomyogenic, vasculogenic and/or fibrogenic c-kit-positive cells and a category of c-kit-positive cells that retains an undifferentiated state within the damaged heart.

[Relapsed/refractory multiple myeloma with CD138 shedding and formation of extramedullary disease in the common bile duct region presenting as obstructive jaundice].

A 56-year-old man was diagnosed with immunoglobulin (Ig) A-κ multiple myeloma in July 2007. After three courses of vincristine, adriamycin, and dexamethasone (VAD) chemotherapy, autologous peripheral blood stem cell transplantation was performed and achieved a very good partial response. In February 2010, an increase in the M-protein concentration and plasmacytoma in the L3/4 lumbar vertebrae were observed, and radiation treatment was performed. This was followed by administrations of bortezomib, lenalidomide, and thalidomide, none of which achieved a good response. In November 2011, the patient presented with obstructive jaundice, and imaging tests revealed tumorous lesions in the lower bile duct region and bilateral kidneys. Plasmacytoma was diagnosed from biopsy of the right renal mass. Radiotherapy to the common bile duct tumor resulted in jaundice amelioration, but the patient died despite subsequent treatment efforts. Autopsy revealed multiple extramedullary lesions in the abdominal cavity and in the region around the common bile duct. CD138 shedding was observed in the myeloma cells. We include a discussion of the literature on CD138 shedding and 38 reports of obstructive jaundice associated with extramedullary disease.

How do resident stem cells repair the damaged myocardium?

It has been a decade since the monumental discovery of resident stem cells in the mammalian heart, and the following studies witnessed the continuous turnover of cardiomyocytes and vascular cells, maintaining the homeostasis of the organ. Recently, the autologous administration of c-kit-positive cardiac stem cells in patients with ischemic heart failure has led to an incredible outcome; the left ventricular ejection fraction of the cell-treated group improved from 30% at the baseline to 38% after one year and to 42% after two years of cell injection. The potential underlying mechanisms, before and after cell infusion, are explored and discussed in this article. Some of them are related to the intrinsic property of the resident stem cells, such as direct differentiation, paracrine action, and immunomodulatory function, whereas others involve environmental factors, leading to cellular reverse remodeling and to the natural selection of "juvenile" cells. It has now been demonstrated that cardiac stem cells for therapeutic purposes can be prepared from tiny biopsied specimens of the failing heart as well as from frozen tissues, which may remarkably expand the repertoire of the strategy against various cardiovascular disorders, including non-ischemic cardiomyopathy and congenital heart diseases. Further translational investigations are needed to explore these possibilities.

Cardiac stem cell niches.

The critical role that stem cell niches have in cardiac homeostasis and myocardial repair following injury is the focus of this review. Cardiac niches represent specialized microdomains where the quiescent and activated state of resident stem cells is regulated. Alterations in niche function with aging and cardiac diseases result in abnormal sites of cardiomyogenesis and inadequate myocyte formation. The relevance of Notch1 signaling, gap-junction formation, HIF-1α and metabolic state in the regulation of stem cell growth and differentiation within the cardiac niches are discussed.

Myocyte renewal and therapeutic myocardial regeneration using various progenitor cells.

Whereas the demand on effective treatment options for chronic heart failure is dramatically increasing, the recent recognition of physiological and pathological myocyte turnover in the adult human heart provided a fundamental basis for the therapeutic regeneration. Divergent modalities were experimentally introduced to this field, and selected ones have been applied clinically; the history began with skeletal myoblasts and bone-marrow-derived cells, and lately mesenchymal stem/stromal cells and resident cardiac cells joined the repertoire. Among them, autologous transplantation of c-kit-positive cardiac stem cells in patients with chronic ventricular dysfunction resulted in an outstanding outcome with long-lasting effects without increasing major adverse events. To further optimize currently available approaches, we have to consider multiple factors, such as the targeting disease, the cell population and number to be administered, and the timing and the route of cell delivery. Exploration of the consequence of the previous clinical trials would allow us to envision an ideal cellular therapy for various cardiovascular disorders.